There is currently a lack of knowledge and understanding of those independent and interrelated factors which control the blood- materials interactions and the healing and repair processes which are initiated when cardiovascular materials are implanted. This study is directed toward obtaining a better understanding of blood-materials and tissue-materials interactions utilizing human synthetic vascular grafts and other important biomaterials as models for these interactions. Studies in this proposal focus on elucidating those parameters whichare important in the human blood-materials interactions of cardiovascular materials and the tissue response and healing of human vascular grafts. The pseudointima of retrieved human vascular grafts will be investigated biochemically for the present, distribution and quantities of collagens (V, III, I), glycosaminoglycans, and fibrin-fibrinogen complexes. Studies on human blood-materials interactions of cardiovascular materials will be carried out in an in vitro human blood recirculation system. Studies will be directed toward developing a better understanding of protein adsorption and hemostatic mechanisms, platelet interactions, and complement activation and neutrophil adhesion by synthetic vascular grafts currently in use clinically and other important biomaterials. Protein adsorption studies will focus on the determination of the surface composition of the adsorbed protein layer and its interaction with circulating blood and its components. The platelet interaction studies will be directed toward differentiating between bulk (circulating) activation and surface activation, platelet-fibrinogen interactions through fibrinogen receptors on platelets, and the variation in cytosolic messengers within platelets when platelets are activated. Neutrophil activation and release studies will focus on the release of toxic oxygen metabolites which may alter the composition of the pseudointima on human vascular grafts. Complement activation studies will be carried out concurrently. The utilization of clinically important biomedical polymers in our studies coupled with the elucidation of human blood and tissue interactions with these materials and vascular grafts will provide a more fundamental understanding of biological processes important to the success or failure of cardiovascular materials. Our long-term goal is the development of a body of knowledge which will be utilized for the development of biomaterials where human blood and tissue interactions are important.